Increases in Brain 1H-MR Glutamine and Glutamate Signals Following Acute Exhaustive Endurance Exercise in the Rat

Abstract

Objective: Proton magnetic resonance spectroscopy (1H-MRS) in ultra-high magnetic field can be used for non-invasive quantitative assessment of brain glutamate (Glu) and glutamine (Gln) in vivo. Glu, the main excitatory neurotransmitter in the central nervous system, is efficiently recycled between synapses and presynaptic terminals through Glu-Gln cycle which involves glutamine synthase confined to astrocytes, and uses 60–80% of energy in the resting human and rat brain. During voluntary or involuntary exercise many brain areas are significantly activated, which certainly intensifies Glu-Gln cycle. However, studies on the effects of exercise on 1H-MRS Glu and/or Gln signals from the brain provided divergent results. The present study on rats was performed to determine changes in 1H-MRS signals from three brain regions engaged in motor activity consequential to forced acute exercise to exhaustion.Method: After habituation to treadmill running, rats were subjected to acute treadmill exercise continued to exhaustion. Each animal participating in the study was subject to two identical imaging sessions performed under light isoflurane anesthesia, prior to, and following the exercise bout. In control experiments, two imaging sessions separated by the period of rest instead of exercise were performed. 1H-NMR spectra were recorded from the cerebellum, striatum, and hippocampus using a 7T small animal MR scanner.Results: Following exhaustive exercise statistically significant increases in the Gln and Glx signals were found in all three locations, whereas increases in the Glu signal were found in the cerebellum and hippocampus. In control experiments, no changes in 1H-MRS signals were found.Conclusion: Increase in glutamine signals from the brain areas engaged in motor activity may reflect a disequilibrium caused by increased turnover in the glutamate-glutamine cycle and a delay in the return of glutamine from astrocytes to neurons. Increased turnover of Glu-Gln cycle may be a result of functional activation caused by forced endurance exercise; the increased rate of ammonia detoxification may also contribute. Increases in glutamate in the cerebellum and hippocampus are suggestive of an anaplerotic increase in glutamate synthesis due to exercise-related stimulation of brain glucose uptake. The disequilibrium in the glutamate-glutamine cycle in brain areas activated during exercise may be a significant contributor to the central fatigue phenomenon.

GABA concentration in sensorimotor cortex following high‐intensity exercise and relationship to lactate levels

“…Interestingly, a 7T MRS study in which rats were exercised to exhaustion revealed greater increases in glutamine relative to glutamate (Swiatkiewicz et al . ). Nonetheless, we note that Dennis et al .…”

Exercise-Induced Fatigue Impairs Bidirectional Corticostriatal Synaptic Plasticity

“…For instance, Guezennec et al ( 1998 ) reported the Glu level was reduced after exhaustion in the striatum of rats. Świątkiewicz et al ( 2017 ) using proton magnetic resonance spectroscopy technique showed that the Glu signal was increased in the cerebellum and hippocampus, but not changed in the striatum of rats following acute exhaustive exercise. However, Liu et al ( 2011 ) reported that the content of Glu was significantly increased in rat’s telencephalon after EF.…”

Randomized controlled trial evaluating the temporal effects of high‐intensity exercise on learning, short‐term and long‐term memory, and prospective memory

“…In addition to the population (fewer studies in young adults) and potential temporal effects of exercise on memory, three additional gaps in the literature include the exercise stimulus, memory type, and memory follow‐up period. With regard to the exercise stimulus, and despite animal work demonstrating that high‐intensity exercise is effective in increasing post‐synaptic excitatory activity (Swiatkiewicz et al ., ) and long‐term memory (Wang & Wang, ), the majority of research in the young adult population (Miles & Hardman, ; Libkuman et al ., ; Covassin et al ., ; Sibley & Beilock, ; Labban & Etnier, ; Berman et al ., ; Gothe et al ., ; Nanda et al ., ; Basso et al ., ; Loprinzi & Kane, ; McNerney & Radvansky, ; Bantoft et al ., ; Hwang et al ., ) has employed moderate‐intensity exercise protocols. Regarding memory type, all of the studies in the young adult population (Miles & Hardman, ; Libkuman et al ., ; Covassin et al ., ; Sibley & Beilock, ; Labban & Etnier, ; Berman et al ., ; Gothe et al ., ; Nanda et al ., ; Basso et al ., ; Loprinzi & Kane, ; McNerney & Radvansky, ; Bantoft et al ., ; Hwang et al ., ) have examined either retrospective‐related episodic memory, recognition memory, logical memory, working memory, long‐term memory, visuospatial memory, or verbal memory.…”